This project, in part, represents an extension of work previously reported as Project Number Z01 DK69037. Glomerular function was measured initially over a 4-year period in 194 Pima Indians selected to represent stages in the development and progression of diabetic renal disease. Eighty-six of these subjects had type 2 diabetes and micro- or macroalbuminuria. Subjects underwent serial determinations of albuminuria and GFR. Many of these subjects continue to be followed and we have accumulated over 19 years of data on glomerular hemodynamic function in these patients. We also follow a population-based cohort of Pima Indians who are invited every two years to participate in a research examinination. The methods for this longitudinal study are described in detail in Project Numbers Z01 DK069097-01 and Z01 DK069000-42. Urinary albumin-to-creatinine ratios and serum creatinine concentration are measured at each of these examinations, and participants who progress to kidney failure are identified.[unreadable] [unreadable] In the past year, we described the effect of youth-onset type 2 diabetes on the appearance of kidney failure and mortality in mid-life (ages 25-54 years). We found that the incidence of end-stage renal disease in mid-life in Pima Indians with diabetes diagnosed before 20 years of age was five times as high as in those that developed diabetes as adults. The death rate in the youth-onset group was 3 times as high as in nondiabetic subjects of the same age distribution. We found that periodontal disease predicts the development of proteinuria and end-stage renal disease, adding to the list of diabetic complications to which periodontitis is related. We used urine proteomic profiling to identify diabetic Pima Indians at risk for diabetic nephropathy before they developed elevated urinary albumin excretion, and studies are underway to identify the specific proteins involved in this early prediction using a number of different methodologies. We demonstrated that despite an increasing incidence of proteinuria, attributable in large part to an increasing average duration of diabetes in the study population, the incidence of end-stage renal disease is declining, suggesting that improvements in patient management are favorably impacting the progression of diabetic kidney disease in this population.[unreadable] [unreadable] In the coming year, we will characterize, among other things, the frequency and impact of low glomerular filtration rate in diabetic persons with normal urinary albumin excretion to determine whether these persons are at different risk for progression of kidney disease than those with elevated urinary albumin excretion. We will examine the effect of alcohol intake on development and progression of diabetic kidney disease and determine the predictive value of elevated urinary albumin excretion for progressive kidney disease in children and adolescents. Changes in management of diabetic kidney disease will be examined to determine whether improvements in health services are reflected by improvements in blood pressure, glycemic, and lipid control. Changes in glomerular hemodynamics will be examined relative to structural damage identified by morphometric evaluation of kidney biopsies as reported in Project Number Z01 DK069100-01.[unreadable] [unreadable] This project continues to yield new insights into the pathogenesis, course, and management of kidney disease in type 2 diabetes. Characterization of hemodynamic function over prolonged periods, combined with detailed clinical information derived from ongoing epidemiologic evaluation have greatly enriched the value of this data resource for studying diabetic kidney disease.